title: Variant surface antigens of malaria parasites: functional and evolutionary insights from comparative gene family classification and analysis.
abstract: BACKGROUND
  Plasmodium parasites, the causative agents of malaria, express many variant antigens on cell surfaces. Variant surface antigens (VSAs) are typically organized into large subtelomeric gene families that play critical roles in virulence and immune evasion. Many important aspects of VSA function and evolution remain obscure, impeding our understanding of virulence mechanisms and vaccine development. To gain further insights into VSA function and evolution, we comparatively classified and examined known VSA gene families across seven Plasmodium species.
  
  
  RESULTS
  We identified a set of ultra-conserved orthologs within the largest Plasmodium gene family pir, which should be considered as high-priority targets for experimental functional characterization and vaccine development. Furthermore, we predict a lipid-binding domain in erythrocyte surface-expressed PYST-A proteins, suggesting a role of this second largest rodent parasite gene family in host cholesterol salvage. Additionally, it was found that PfMC-2TM proteins carry a novel and putative functional domain named MC-TYR, which is conserved in other P. falciparum gene families and rodent parasites. Finally, we present new conclusive evidence that the major Plasmodium VSAs PfEMP1, SICAvar, and SURFIN are evolutionarily linked through a modular and structurally conserved intracellular domain.
  
  
  CONCLUSIONS
  Our comparative analysis of Plasmodium VSA gene families revealed important functional and evolutionary insights, which can now serve as starting points for further experimental studies.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Frech
authors.forename: Nansheng
authors.initials: N
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics; D016000:Cluster Analysis; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D023281:Genomics; D042541:Intracellular Space / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008288:Malaria; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000166:cytology / Q000235:genetics* / Q000276:immunology; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014364:Tryptophan
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015800:Protozoan Proteins; D014364:Tryptophan